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Abstract Despite the recent progress on the solution-phase enzymatic synthesis of heparan sulfate (HS) and chondroitin sulfate (CS), solid-phase enzymatic synthesis has not been fully investigated. Here, we describe the solid-phase enzymatic synthesis of HS and CS backbone oligosaccharides using specialized linkers. We demonstrate the use of immobilized HS linker to synthesize CS, and the use of immobilized CS linker to synthesize HS. The linkers were then digested with chondroitin ABCase and heparin lyases, respectively, to obtain the products. Our findings uncover a potential approach for accelerating the synthesis of structurally homogeneous HS and CS oligosaccharides.
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Expedient Synthesis of a Library of Heparan Sulfate‐Like “Head‐to‐Tail” Linked Multimers for Structure and Activity Relationship Studies**
Abstract Heparan sulfate (HS) plays important roles in many biological processes. The inherent complexity of naturally existing HS has severely hindered the thorough understanding of their structure‐activity relationship. To facilitate biological studies, a new strategy has been developed to synthesize a HS‐like pseudo‐hexasaccharide library, where HS disaccharides were linked in a “head‐to‐tail” fashion from the reducing end of a disaccharide module to the non‐reducing end of a neighboring module. Combinatorial syntheses of 27 HS‐like pseudo‐hexasaccharides were achieved. This new class of compounds bound with fibroblast growth factor 2 (FGF‐2) with similar structure‐activity trends as HS oligosaccharides bearing native glycosyl linkages. The ease of synthesis and the ability to mirror natural HS activity trends suggest that the new head‐to‐tail linked pseudo‐oligosaccharides could be an exciting tool to facilitate the understanding of HS biology.
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- Award ID(s):
- 1933525
- PAR ID:
- 10380802
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 61
- Issue:
- 48
- ISSN:
- 1433-7851
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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